Denervated frog muscle shows altered calcium content and contractile kinetics as the earliest functional consequences of loss of nervous influences. Our hypothesis is that several types of changes--strength, ionic fluxes, contractile inactivation and relaxation, transmitter sensitivity--are linked through the calcium regulatory mechanisms of the muscles. We propose to characterize changes in calcium regulation and contractile dynamics and to relate them to the larger pattern of denervation sequelae by means of: 1) studies of contractile inactivation and post-tetanic potentiation in single mammalian muscle fibers; 2) fast time resolution of sarcolemmal, transverse tubular, and cisternal calcium exchange pools in single muscle fibers by means of radiocalcium tracer studies; 3) study of linkage of sodium and calcium flux mechanisms; 4) sequential appearance of calcium pool changes in mammalian muscle following denervation. Both frog and mouse muscle preparations characterized as to contractile and metabolic type will be used. Our study will: 1) extend knowledge of excitation-contraction coupling in muscle; 2) contribute directly to understanding of changes in traumatically denervated muscle; and 3) develop a framework for studying groups of functional alterations which can be applied to other disease states of muscle, particularly those involving sarcotubular changes.